Novel Experimental Drugs for Treatment of Multiple Myeloma

References

• National Cancer Institute. Cancer stat facts: myeloma. Available from: https://seer.cancer.gov/statfacts/html/mulmy.html. Accessed Dec 01, 2020.
   Google Scholar
• Anderson KC. Progress and paradigms in multiple myeloma. Clin Cancer Res. 2016;22:5419–5427. doi:10.1158/1078-0432.CCR-16-0625
   PubMed Web of Science ®Google Scholar
• Kumar SK, Rajkumar SV, Dispenzieri A, et al. Improved survival in multiple myeloma and the impact of novel therapies. Blood. 2008;111:2516–2520. doi:10.1182/blood-2007-10-116129
   PubMed Web of Science ®Google Scholar
• Kumar SK, Dispenzieri A, Lacy MQ, et al. Continued improvement in survival in multiple myeloma: changes in early mortality and outcomes in older patients. Leukemia. 2014;28:1122–1128. doi:10.1038/leu.2013.313
   PubMed Web of Science ®Google Scholar
• Kronke J, Udeshi ND, Narla A, et al. Lenalidomide causes selective degradation of IKZF1 and IKZF3 in multiple myeloma cells. Science. 2014;343:301–305. doi:10.1126/science.1244851
   PubMed Web of Science ®Google Scholar
• Davies F, Baz R. Lenalidomide mode of action: linking bench and clinical findings. Blood Rev. 2010;24(Suppl 1):S13–S19. doi:10.1016/S0268-960X(10)70004-7
   PubMed Web of Science ®Google Scholar
• Chauhan D, Hideshima T, Mitsiades C, et al. Proteasome inhibitor therapy in multiple myeloma. Mol Cancer Ther. 2005;4:686–692. doi:10.1158/1535-7163.MCT-04-0338
   PubMed Web of Science ®Google Scholar
• Hideshima T, Mitsiades C, Akiyama M, et al. Molecular mechanisms mediating antimyeloma activity of proteasome inhibitor PS-341. Blood. 2003;101:1530–1534. doi:10.1182/blood-2002-08-2543
   PubMed Web of Science ®Google Scholar
• Ito S. Proteasome inhibitors for the treatment of multiple myeloma. Cancers. 2020;12:265. doi:10.3390/cancers12020265
   PubMed Web of Science ®Google Scholar
• Moreau P, San Miguel J, Sonneveld P, et al. Multiple myeloma: ESMO clinical practice guidelines for diagnosis, treatment and follow-up. Ann Oncol. 2017;28(Suppl. 4):iv52–iv61. doi:10.1093/annonc/mdx096
   PubMed Web of Science ®Google Scholar
• Mikhael J, Ismaila N, Cheung MC, et al. Treatment of multiple myeloma: ASCO and CCO joint clinical practice guidelines. J Clin Oncol. 2019;37:1228–1263. doi:10.1200/JCO.18.02096
   PubMed Web of Science ®Google Scholar
• Nandakumar B, Kapoor P, Binder M, et al. Continued improvement in survival of patients with newly diagnosed multipole myeloma. Blood. 2020;136(Suppl. 1):abstract 2280. doi:10.1182/blood-2020-140388
   Web of Science ®Google Scholar
• Kumar SK, Dimopoulos MA, Kastritis E, et al. Natural history of relapsed myeloma, refractory to immunomodulatory drugs and proteasome inhibitors: a multicenter IMWG study. Leukemia. 2017;31:2443–2448. doi:10.1038/leu.2017.138
   PubMed Web of Science ®Google Scholar
• Coiffier B, Thieblemont C, Van Den Neste E, et al. Long-term outcome of patients in the LNH-98.5 trial, the first randomized study comparing rituximab-CHOP to standard CHOP chemotherapy in DLBCL patients: a study by the Groupe d’Etudes des Lymphomes de l’Adulte. Blood. 2010;116:2040–2045. doi:10.1182/blood-2010-03-276246
   PubMed Web of Science ®Google Scholar
• Connors JM, Jurczak W, Strauss DJ, et al. Brentuximab vedotin with chemotherapy for stage III or IV Hodgkin’s lymphoma. N Engl J Med. 2018;378:331–344. doi:10.1056/NEJMoa1708984
   PubMed Web of Science ®Google Scholar
• Offidani M, Corvatta L. A review discussing elotuzumab and its use in the second-line plus treatment of multiple myeloma. Future Oncol. 2018;14:319–329. doi:10.2217/fon-2017-0371
   PubMed Web of Science ®Google Scholar
• Lonial S, Dimopoulos MA, Palumbo A, et al. Elotuzumab therapy for relapsed or refractory multiple myeloma. N Engl J Med. 2015;373:621–631. doi:10.1056/NEJMoa1505654
   PubMed Web of Science ®Google Scholar
• Dimopoulos MA, Dytfeld D, Grosicki S, et al. Elotuzumab plus pomalidomide and dexamethasone for multiple myeloma. N Engl J Med. 2018;379:1811–1822. doi:10.1056/NEJMoa1805762
   PubMed Web of Science ®Google Scholar
• Dimopoulos MA, Lonial S, Betts KA, et al. Elotuzumab plus lenalidomide and dexamethasone in relapsed/refractory multiple myeloma: extended 4-year follow-up and analysis of relative progression-free survival from the randomized ELOQUENT-2 trial. Cancer. 2018;124:4032–4043. doi:10.1002/cncr.31680
   PubMed Web of Science ®Google Scholar
• Dimopoulos MA, Lonial S, White D, et al. Elotuzumab, lenalidomide and dexamethasone in RRMM: final overall survival results from the Phase 3 randomized ELOQUENT-2 study. Blood Cancer J. 2020;10:91. doi:10.1038/s41408-020-00357-4
   PubMed Web of Science ®Google Scholar
• Bristol-Myers Squibb. Bristol-Myers Squibb reports primary results of ELOQUENT-1 study evaluating Empliciti (elotuzumab) plus Revlimid (lenalidomide) and dexamethasone in patients with newly diagnosed, untreated multiple myeloma. Available from: https://news.bms.com/news/corporate-financial/2020/Bristol-Myers-Squibb-Reports-Primary-Results-of-ELOQUENT-1-Study-Evaluating-Empliciti-elotuzumab-Plus-Revlimid-lenalidomide-and-Dexamethasone-in-Patients-with-Newly-Diagnosed-Untreated-Multiple-Myeloma/default.aspx. Accessed Dec 01, 2020.
   Google Scholar
• Goldschmidt H, Mai EK, Salwender HJ, et al. Bortezomib, lenalidomide and dexamethasone with or without elotuzumab as induction therapy for newly diagnosed, transplant-eligible multiple myeloma. Hemasphere. 2020;4(S1):abstract S 203.
   Google Scholar
• Lokhorst HM, Plesner T, Laubach JP, et al. Targeting CD38 with daratumumab monotherapy in multiple myeloma. New Engl J Med. 2015;373:1207–1219. doi:10.1056/NEJMoa1506348
   PubMed Web of Science ®Google Scholar
• Lonial S, Weiss BM, Usmani SZ, et al. Daratumumab monotherapy in patients with treatment-refractory multiple myeloma (SIRIUS): an open-label, randomised, phase 2 trial. Lancet. 2016;387:1551–1560. doi:10.1016/S0140-6736(15)01120-4
   PubMed Web of Science ®Google Scholar
• Nooka AK, Kaufman JL, Hofmeister CC, et al. Daratumumab in multiple myeloma. Cancer. 2019;125:2364–2382. doi:10.1002/cncr.32065
   PubMed Web of Science ®Google Scholar
• Dimopoulos MA, Oriol A, Nahi H, et al. Daratumumab, lenalidomide, and dexamethasone for multiple myeloma. New Engl J Med. 2016;375:1319–1331. doi:10.1056/NEJMoa1607751
   PubMed Web of Science ®Google Scholar
• Palumbo A, Chanan-Khan A, Weisel K, et al. Daratumumab, bortezomib, and dexamethasone for multiple myeloma. New Engl J Med. 2016;375:754–766. doi:10.1056/NEJMoa1606038
   PubMed Web of Science ®Google Scholar
• Dimopoulos MA, Terpos E, Boccadoro M, et al. Apollo: phase 3 randomized study of subcutaneous daratumumab plus pomalidomide and dexamethasone (D-Pd) versus pomalidomide and dexamethasone (Pd) alone in patients with relapsed/refractory multiple myeloma. Blood. 2020;136(Suppl 1):abstract 412. doi:10.1182/blood-2020-135874
   Web of Science ®Google Scholar
• Dimopoulos MA, Quach H, Mateos M-V, et al. Carfilzomib, dexamethasone and daratumumab versus carfilzomib and dexamethasone in relapsed or refractory multiple myeloma: updated efficacy and safety results of the phase 3 Candor study. Blood. 2020;136(Suppl 1):abstract 2325. doi:10.1182/blood-2020-137602
   Web of Science ®Google Scholar
• Moreau P, Attal M, Hulin C, et al. Bortezomib, thalidomide, and dexamethasone with or without daratumumab before and after autologous stem-cell transplantation for newly diagnosed multiple myeloma (CASSIOPEIA): a randomised, open-label, phase 3 study. Lancet. 2019;394:29–38. doi:10.1016/S0140-6736(19)31240-1
   PubMed Web of Science ®Google Scholar
• Voorhees PM, Kaufman JL, Laubach J, et al. Daratumumab, lenalidomide, bortezomib, and dexamethasone for transplant-eligible newly diagnosed multiple myeloma: the GRIFFIN trial. Blood. 2020;136:936–945. doi:10.1182/blood.2020005288
   PubMed Web of Science ®Google Scholar
• Mateos MV, Dimopoulos MA, Cavo M, et al. Daratumumab plus bortezomib, melphalan, and prednisone for untreated myeloma. N Engl J Med. 2018;378:518–528. doi:10.1056/NEJMoa1714678
   PubMed Web of Science ®Google Scholar
• Kumar SK, Facon T, Usmani SZ, et al. Updated analysis of daratumumab plus lenalidomide and dexamethasone (D-Rd) versus lenalidomide and dexamethasone (Rd) in patients with transplant-ineligible newly diagnosed multiple myeloma: the phase 3 Maia study. Blood. 2020;136(Suppl 1):abstract 2276. doi:10.1182/blood-2020-134847
   Web of Science ®Google Scholar
• Mateos MV, Nahi H, Legiec W, et al. Subcutaneous versus intravenous daratumumab in patients with relapsed or refractory multiple myeloma (COLUMBA): a multicentre, open-label, non-inferiority, randomised, phase 3 trial. Lancet Haematol. 2020;7:e370–e380. doi:10.1016/S2352-3026(20)30070-3
   PubMed Web of Science ®Google Scholar
• Chari A, Rodriguez-Otero P, McCarthy H, et al. Subcutaneous daratumumab plus standard treatment regimens in patients with multiple myeloma across lines of therapy (PLEIADES): and open-label Phase II study. Br J Haematol. 2020
   Web of Science ®Google Scholar
• Van de Domnk NW, Usmani SZ. CD38 antibodies in multiple myeloma: mechanisms of action and modes of resistance. Front Immunol. 2018;9:2134. doi:10.3389/fimmu.2018.02134
   Web of Science ®Google Scholar
• Van Bueren JL, Jakobs D, Kaldenhoven N, et al. Direct in vitro comparison of daratumumab with surrogate analogs of CD38 antibodies MOR03087, SAR650884 and Ab79. Blood. 2014;124(21):abstract 3474. doi:10.1182/blood.V124.21.3474.3474
   Web of Science ®Google Scholar
• Feng X, Zhang L, Acharya C, et al. Targeting CD38 suppresses induction and function of T regulatory cells to mitigate immunosuppression in multiple myeloma. Clin Cancer Res. 2017;23:4290–4300. doi:10.1158/1078-0432.CCR-16-3192
   PubMed Web of Science ®Google Scholar
• Martin TG, Corzo K, Chiron M, et al. Therapeutic opportunities with pharmacological inhibition of CD38 with isatuximab. Cells. 2019;8:1522. doi:10.3390/cells8121522
   PubMed Web of Science ®Google Scholar
• Attal M, Richardson PG, Rajkumar SV, et al. Isatuximab plus pomalidomide and low-dose dexamethasone versus pomalidomide and low-dose dexamethasone in patients with relapsed and refractory multiple myeloma (ICARIA-MM): a randomised, multicentre, open-label, phase 3 study. Lancet. 2019;394:2096–2107. doi:10.1016/S0140-6736(19)32556-5
   PubMed Web of Science ®Google Scholar
• Schjesvold F, Bringhen S, Richardson PG, et al. Isatuximab plus pomalidomide and dexamethasone in frail patients with relapsed/refractory multiple myeloma: icaria-MM subgroup analysis. Blood. 2020;136(Suppl 1):abstract 1411.
   Google Scholar
• Moreau P, Dimopoulos MA, Mikhael J, et al. Isatuximab plus carfilzomib and dexamethasone vs carfilzomib and dexamethasone in relapsed/ refractory multiple myeloma (IKEMA): interim analysis of a phase 3, randomized, open-label study. Blood. 2020;136(Suppl 1):abstract 2316. doi:10.1182/blood.2020008150
   Web of Science ®Google Scholar
• Martin T, Mikhael J, Hajek R, et al. Depth of response and response kinetics of isatuximab plus carfilzomib and dexamethasone in relapsed/refractory multiple myeloma: IKEMA interim analysis. Blood. 2020;136(Suppl 1):abstract 414. doi:10.1182/blood-2020-137681
   Web of Science ®Google Scholar
• Weisel KC, Asemissen AM, Besemer B, et al. Depth of response to isatuximab, carfilzomib, lenalidomide and dexamethasone (Isa-KRd) in front-line treatment of high-risk multiple myeloma: interim analysis of the GMMG-CONCEPT trial. J Clin Oncol. 2020;38(Suppl.):abstract 8505. doi:10.1200/JCO.2020.38.15_suppl.8508
   Google Scholar
• Ocio EM, Bringhen S, Oliva S, et al. Updates from a phase Ib study of isatuximab, bortezomib, and dexamethasone plus cyclophosphamide or lenalidomide in transplant ineligible newly diagnosed multiple myeloma. Blood. 2020;136(Suppl 1):abstract 2288. doi:10.1182/blood-2020-136569
   Web of Science ®Google Scholar
• Raab MS, Engelhardt M, Blank A, et al. MOR202, a novel anti-CD38 monoclonal antibody, in patients with relapsed or refractory multiple myeloma: a first-in-human, multicenter, phase 1-2a trial. Lancet Hematol. 2020;7:e381–394. doi:10.1016/S2352-3026(19)30249-2
   PubMed Web of Science ®Google Scholar
• Ghobrial IM, Liu C-J, Redd R, et al. A phase Ib/II trial of the first-in-class anti-CXCR4 antibody ulocuplumab in combination with lenalidomide or bortezomib plus dexamethasone in relapsed multiple myeloma. Clin Cancer Res. 2020;26:344–353. doi:10.1158/1078-0432.CCR-19-0647
   PubMed Web of Science ®Google Scholar
• Franssen LE, Stege CAM, Zweegman S, et al. Resistance mechanisms towards CD38-directed antibody therapy in multiple myeloma. J Clin Med. 2020;9:1195. doi:10.3390/jcm9041195
   Web of Science ®Google Scholar
• Paul B, Symanowski J, Osipoff P, et al. A phase 2 trial of daratumumab and pembrolizumab in refractory multiple myeloma. Blood. 2020;136(Suppl 1):abstract 1399. doi:10.1182/blood-2020-141623
   Web of Science ®Google Scholar
• Kambhampati S, Wong SW, Martin T, et al. Phase II study of daratumumab in combination with azacitidine and dexamethasone in relapsed/refractory multiple myeloma previously treated with daratumumab: darazadex. Blood. 2020;136(Suppl 1):abstract 2326. doi:10.1182/blood-2020-138869
   Web of Science ®Google Scholar
• Perez De Acha O, Idler BI, Walker ZJ, et al. Myeloma drug sensitivity testing to optimize retreatment with anti-CD38 monoclonal antibodies in daratumumab-refractory patients. Blood. 2020;136(Suppl 1):abstract 1387. doi:10.1182/blood-2020-137819
   Web of Science ®Google Scholar
• Gandhi UH, Cornell RF, Lakshman A, et al. Outcomes of patients with multiple myeloma refractory to CD38-targeted monoclonal antibody therapy. Leukemia. 2019;33:2266–2275. doi:10.1038/s41375-019-0435-7
   PubMed Web of Science ®Google Scholar
• Dalla Palma B, Marchica V, Catarozzo MT, Giuliani N, Accardi F. Monoclonal and bispecific anti-BCMA antibodies in multiple myeloma. J Clin Med. 2020;9:3022. doi:10.3390/jcm9093022
   Web of Science ®Google Scholar
• Tai Y-T, Li XF, Breitkreutz I, et al. Role of B-cell–activating factor in adhesion and growth of human multiple myeloma cells in the bone marrow microenvironment. Cancer Res. 2006;66:6675–6682. doi:10.1158/0008-5472.CAN-06-0190
   PubMed Web of Science ®Google Scholar
• Moreaux J, Legou E, Jourdan E, et al. BAFF and APRIL protect myeloma cells from apoptosis induced by interleukin 6 deprivation and dexamethasone. Blood. 2004;103:3148–3157. doi:10.1182/blood-2003-06-1984
   PubMed Web of Science ®Google Scholar
• Lancman G, Richter J, Chari A. Bispecific, trispecific, and other novel immune treatments in myeloma. Hematology. 2020;2020:264–271. doi:10.1182/hematology.2020000110
   Web of Science ®Google Scholar
• Topp MS, Duell J, Zugmaier G, et al. Anti-B-cell maturation antigen BiTE molecule AMG 420 induces responses in multiple myeloma. J Clin Oncol. 2020;38:775–778. doi:10.1200/JCO.19.02657
   PubMed Web of Science ®Google Scholar
• Harrison JS, Minnema MC, Lee HC, et al. A phase 1 first in Human (FIH) study of AMG 701, an anti-B-Cell maturation antigen (BCMA) half-life extended (HLE) BiTE® (bispecific T-cell engager) molecule, in relapsed/refractory (RR) multiple myeloma (MM). Blood. 2020;136(Suppl 1):abstract 181. doi:10.1182/blood-2020-134063
   Web of Science ®Google Scholar
• Usmani SZ, Mateos M-V, Nahi H, et al. Phase I study of teclistamab, a humanized B-cell maturation antigen (BCMA) x CD3 bispecific antibody, in relapsed/ refractory multiple myeloma (R/R MM). J Clin Oncol. 2020;38(Suppl.):abstract 100. doi:10.1200/JCO.2020.38.15_suppl.100
   Web of Science ®Google Scholar
• Garfall AL, Usmani SZ, Mateos M-V, et al. Updated phase 1 results of teclistamab, a B-Cell Maturation Antigen (BCMA) x CD3 bispecific antibody, in relapsed and/or refractory multiple myeloma (RRMM). Blood. 2020;136(Suppl 1):abstract 27. doi:10.1182/blood-2020-138831
   Web of Science ®Google Scholar
• Costa LJ, Wong SW, Bermudez A, et al. First clinical study of the B-Cell Maturation Antigen (BCMA) 2+1 cell engager CC-93269 in patients with relapsed/refractory multiple myeloma: interim results of a phase 1 multicenter trial. Blood. 2019;134(Suppl. 1):abstract 143. doi:10.1182/blood-2019-122895
   Web of Science ®Google Scholar
• Atamaniuk J, Gleiss A, Porpaczy E, et al. Overexpression of G protein coupled receptor 5D in the bone marrow is associated with poor prognosis in patients with multiple myeloma. Eur J Clin Invest. 2012;42:953–960. doi:10.1111/j.1365-2362.2012.02679.x
   PubMed Web of Science ®Google Scholar
• Chari A, Berdeja JG, Oriol A, et al. A phase 1, first-in-human study of Talquetamab, a G Protein-Coupled Receptor Family C Group 5 Member D (GPRC5D) x CD3 bispecific antibody, in patients with relapsed and/or refractory multiple myeloma (RRMM). Blood. 2020;136(Suppl 1):abstract 290. doi:10.1182/blood-2020-133873
   Web of Science ®Google Scholar
• Cohen AD, Harrison SJ, Krishnan A, et al. Initial clinical activity and safety of BFCR4350A, a FcRH5/CD3 T-Cell-Engaging bispecific antibody, in relapsed/ refractory multiple myeloma. Blood. 2020;136(Suppl 1):abstract 292. doi:10.1182/blood-2020-136985
   Web of Science ®Google Scholar
• Sheikh S, Lebel E, Trudel S. Belantamab mafodotin in the treatment of relapsed or refractory multiple myeloma. Fut Oncol. 2020;16:2783–2798. doi:10.2217/fon-2020-0521
   Web of Science ®Google Scholar
• Trudel S, Lendvai N, Popat R, et al. Antibody–drug conjugate, GSK2857916, in relapsed/refractory multiple myeloma: an update on safety and efficacy from dose expansion phase I study. Blood Cancer J. 2019;9:37. doi:10.1038/s41408-019-0196-6
   PubMed Web of Science ®Google Scholar
• Lonial S, Lee HC, Badros A, et al. Belantamab mafodotin for relapsed or refractory multiple myeloma (DREAMM-2): a two-arm, randomised, open-label, phase 2 study. Lancet Oncol. 2020;21:207–221. doi:10.1016/S1470-2045(19)30788-0
   PubMed Web of Science ®Google Scholar
• Lonial S, Nooka A, Thulasi P, et al. Recovery of ocular events with longer-term follow-up in the DREAMMM-2 Study of single-agent belantamab mafodotin (Belamaf) in patients with relapsed or refractory multiple myeloma (RRMM). Blood. 2020;136(Suppl. 1):abstract 3224. doi:10.1182/blood-2020-140078
   Web of Science ®Google Scholar
• Popat R, Lonial S, Voorhees PM, et al. DREAMM-2: single-agent belantamab mafodotin (Belamaf) effects on patient-reported outcome (PRO) measures in patients with relapsed/refractory multiple myeloma (RRMM). Blood. 2020;136(Suppl. 1):abstract 2278.
   Google Scholar
• Nooka A, Lee HC, Badros AZ, et al. Infusion-related reactions (IRRs) in the DREAMM-2 study of single-agent belantamab mafodotin (Belamaf) in patients with relapsed/refractory multiple myeloma (RRMM). Blood. 2020;(Suppl. 1):abstract 3221.
   Google Scholar
• Trudel S, McCurdy A, Sutherland HJ, et al. Part 1 results of a dose finding study of belantamab mafodotin (GSK2857916) in combination with pomalidomide and dexamethasone for the treatment of relapsed/refractory multiple myeloma. Blood. 2020;(Suppl. 1):abstract 725.
   Google Scholar
• Sadelain M, Brentjens R, Riviere I. The basic principles of chimeric antigen receptor design. Cancer Discov. 2013;3:338–398. doi:10.1158/2159-8290.CD-12-0548
   Web of Science ®Google Scholar
• Guedan S, Calderon H, Posey AD, Maus MV. Engineering and design of chimeric antigen receptors. Mol Ther Methods Clin Dev. 2018;12:145–156. doi:10.1016/j.omtm.2018.12.009
   PubMed Web of Science ®Google Scholar
• Mikkilinemi L, Kochenderfer JN. Chimeric antigen receptor T-cell therapies for multiple myeloma. Blood. 2017;130:2594–2602. doi:10.1182/blood-2017-06-793869
   Web of Science ®Google Scholar
• Levine BL, Miskin J, Wonnacott K, Keir C. Global manufacturing of CAR T cell therapy. Mol Ther Methods Clin Dev. 2016;4:92–101. doi:10.1016/j.omtm.2016.12.006
   PubMed Web of Science ®Google Scholar
• Sha UA, Mailankody S. Emerging immunotherapies in multiple myeloma. BMJ. 2020;370:m3176. doi:10.1136/bmj.m3176
   Web of Science ®Google Scholar
• Raje N, Berdeja J, Lin Y, et al. Anti-BCMA CAR T-cell therapy bb2121 in relapsed or refractory multiple myeloma. N Engl J Med. 2019;380:1726–1737. doi:10.1056/NEJMoa1817226
   PubMed Web of Science ®Google Scholar
• Lin Y, Raje NS, Berdeja JG, et al. Idecabtagene vicleucel (ide-cel, bb2121), a BCMA-directed CAR T cell therapy, in patients with relapsed and refractory multiple myeloma: updated results from phase 1 CRB-401 study. Blood. 2020;(Suppl. 1):abstract 131. doi:10.1182/blood.2020006245
   Web of Science ®Google Scholar
• Munshi NC, Anderson LD, Shah N, et al. Idecabtagene vicleucel (ide-cel, bb2121), a BCMA-targeted CAR T cell therapy, in patients with relapsed and refractory multiple myeloma: initial KarMMa results. J Clin Oncol. 2020;38(Suppl.):abstract 8503. doi:10.1200/JCO.2020.38.15_suppl.8503
   Google Scholar
• Berdeja J, Raje NS, Siegel DS, et al. Efficacy and safety of idecabtagene vicleucel (ide-cel, bb2121) in elderly patients with relapsed and refractory multiple myeloma: karMMa subgroup analysis. Blood. 2020;(Suppl. 1):abstract 1367. doi:10.1182/blood.2020007522
   Web of Science ®Google Scholar
• Wang B-Y, Zhao W-H, Liu J, et al. Long-term follow-up of a phase 1, first-in-human open-label study of LCAR-B38M, a structurally differentiated chimeric antigen receptor T (CAR-T) cell therapy targeting B-Cell maturation antigen (BCMA) in patients with relapsed/refractory multiple myeloma. Blood. 2019;134(Suppl. 1):abstract 579. doi:10.1182/blood-2019-124953
   Web of Science ®Google Scholar
• Berdeja JG, Madduri D, Usmani SZ, et al. Update of CARTITUDE-1: a phase 1b/2 study of JNJ-4528, a B-cell maturation antigen (BCMA)-directed ccAR-T cell therapy, in relapsed/ refractory multiple myeloma. J Clin Oncol. 2020;38(Suppl.):abstract 8505. doi:10.1200/JCO.2020.38.15_suppl.8505
   Google Scholar
• Madduri D, Berdeja JG, Usmani SZ, et al. CARTITUDE-1: phase 1b/2 study of ciltacabtagene autoleucel, a B-cell maturation antigen-directed chimeric antigen receptor T cell therapy, in relapsed/ refractory multiple myeloma. Blood. 2020;(Suppl. 1):abstract 177.
   Google Scholar
• Mailankody S, Jakuboviak A, Htut M, et al. Orvacabtagene autoleucel (orva-cel), a B-cell maturation antigen (BCMA)-directed CAR T cell therapy for patients with relapsed/refractory multiple myeloma: update of the phase 1/2 EVOLVE study (NCT03430011). J Clin Oncol. 2020;38(Suppl.):abstract 8504. doi:10.1200/JCO.2020.38.15_suppl.8504
   Google Scholar
• Alsina M, Shah N, Raje NS, et al. Updated results from the phase I CRB-402 study of anti-BCMA CAR-T cell therapy bb21217 in patients with relapsed and refractory multiple myeloma: correlation of expansion and duration of response with T cell phenotypes. Blood. 2020;136(Suppl. 1):abstract 130. doi:10.1182/blood-2020-140410
   Web of Science ®Google Scholar
• Hao S, Jin J, Jiang S, et al. Two-years follow-up of investigator-initiated phase 1 trials of the safety and efficacy of fully human anti-bcma CAR T cells (CT053) in relapsed/ refractory multiple myeloma. Blood. 2020;136(Suppl. 1):abstract 132. doi:10.1182/blood-2020-140156
   Web of Science ®Google Scholar
• Kumar SK, Baz RC, Orlowski RZ, et al. Results from Lummicar-2: a phase 1b/2 study of fully human B-cell maturation antigen-specific CAR T cells (CT053) in patients with relapsed and/or refractory multiple myeloma. Blood. 2020;136(Suppl. 1):abstract 133. doi:10.1182/blood-2020-139802
   Web of Science ®Google Scholar
• Costello VCL, Cohen AD, Patel KK, et al. Phase 1/2 study of the safety and response of P-BCMA-101 CAR-T cells in patients with relapsed/refractory multiple myeloma (PRIME) with novel therapeutic strategies. Blood. 2020;136(Suppl. 1):abstract 134.
   Google Scholar
• Jiang H, Dong B, Gao L, et al. Clinical results of a multicenter study of the first-in-human dual BCMA and CD19 targeted novel platform fast CAR-T cell therapy for patients with relapsed/refractory multiple myeloma. Blood. 2020;136(Suppl. 1):abstract 178. doi:10.1182/blood-2020-138614
   Web of Science ®Google Scholar
• Mailankody S, Matous JV, Liedtke M, et al. Universal: an allogeneic first-in-human study of the anti-BCMA ALLO-715 and the anti-CD52 ALLO-647 in relapsed/ refractory multiple myeloma. Blood. 2020;136(Suppl. 1):abstract 129. doi:10.1182/blood-2020-140641
   Web of Science ®Google Scholar
• Hill R, Cautain B, De Pedro N, et al. Targeting nucleocytoplasmic transport in cancer therapy. Oncotarget. 2014;5:11–28. doi:10.18632/oncotarget.1457
   PubMedGoogle Scholar
• Gravina GL, Senapedis W, McCauley D, et al. Nucleo-cytoplasmic transport as a therapeutic target of cancer. J Hematol Oncol. 2014;7:85. doi:10.1186/s13045-014-0085-1
   PubMed Web of Science ®Google Scholar
• Chari A, Vogl DT, Gavriatopoulou M, et al. Oral selinexor-dexamethasone for triple-class refractory multiple myeloma. N Engl J Med. 2019;381:727–738. doi:10.1056/NEJMoa1903455
   PubMed Web of Science ®Google Scholar
• Bahlis NJ, Sutherland H, White D, et al. Selinexor plus low-dose bortezomib and dexamethasone for patients with relapsed or refractory multiple myeloma. Blood. 2018;132:2546–2554. doi:10.1182/blood-2018-06-858852
   PubMed Web of Science ®Google Scholar
• Grosicki S, Simonova M, Spicka I, et al. Once-per-week selinexor, bortezomib, and dexamethasone versus twice-per-week bortezomib and dexamethasone in patients with multiple myeloma (BOSTON): a randomized, open-label, phase 3 trial. Lancet. 2020;396:1563–1573. doi:10.1016/S0140-6736(20)32292-3
   PubMed Web of Science ®Google Scholar
• Auner HW, Gavriatopoulou M, Delimpasi S, et al. Once weekly selinexor, bortezomib, and dexamethasone versus twice weekly bortezomib and dexamethasone in relapsed or refractory multiple myeloma: age and frailty subgroup analyses from the phase 3 Boston study. Blood. 2020;136(Suppl 1):abstract 3215.
   Google Scholar
• Richard S, Chari A, Delimpasi S, et al. Once weekly selinexor, bortezomib, and dexamethasone versus twice weekly bortezomib and dexamethasone in relapsed or refractory multiple myeloma: high-risk cytogenetic risk planned subgroup analyses from the phase 3 Boston study. Blood. 2020;136(Suppl 1):abstract 1385. doi:10.1182/blood-2020-137154
   Web of Science ®Google Scholar
• Mateos M-V, Gavriatopoulou M, Facon T, et al. Effect of prior treatment with proteasome inhibitors on the efficacy and safety of once weekly selinexor, bortezomib, and dexamethasone in comparison with twice weekly bortezomib and dexamethasone in relapsed or refractory multiple myeloma: subgroup analysis from the Boston study. Blood. 2020;136(Suppl 1):abstract 2297.
   Google Scholar
• Mateos M-V, Jagannath S, Delimpasi S, et al. Effect of prior therapies on the safety and efficacy of once weekly selinexor, bortezomib, and dexamethasone compared with twice weekly bortezomib and dexamethasone in relapsed or refractory multiple myeloma: subgroup analysis from the Boston study. Blood. 2020;136(Suppl 1):abstract 3245.
   Google Scholar
• Gasparetto C, Lipe B, Tuchman SA, et al. Selinexor in combination with carfilzomib and dexamethasone, all once weekly (SKd), for patients with relapsed/refractory multiple myeloma. Blood. 2020;136(Suppl 1):abstract 1366. doi:10.1182/blood-2020-137183
   Web of Science ®Google Scholar
• Chen CI, Bahlis NJ, Gasparetto C, et al. Selinexor in combination with pomalidomide and dexamethasone (SPd) for treatment of patients with relapsed refractory multiple myeloma. Blood. 2020;136(Suppl 1):abstract 726. doi:10.1182/blood-2020-139858
   Web of Science ®Google Scholar
• Chauhan D, Ray A, Viktorsson K, et al. In vitro and in vivo antitumor activity of a novel alkylating agent, melphalan-flufenamide, against multiple myeloma cells. Clin Cancer Res. 2013;19:3019–3031. doi:10.1158/1078-0432.CCR-12-3752
   PubMed Web of Science ®Google Scholar
• Oriol A, Larocca A, Leleu X, et al. Melflufen for relapsed and refractory multiple myeloma. Expert Opin Investig Drugs. 2020;29:1069–1078. doi:10.1080/13543784.2020.1808884
   PubMed Web of Science ®Google Scholar
• Richardson P, Bringhen S, Voorhees P, et al. Melflufen plus dexamethasone in relapsed and refractory multiple myeloma (0-12-M1): a multicenter, international, open-label, phase 1-2 study. Lancet Hematol. 2020;7:e395–e407. doi:10.1016/S2352-3026(20)30044-2
   PubMed Web of Science ®Google Scholar
• Richardson PG, Oriol A, Larocca A, et al. HORIZON (OP-106): melflufen plus dexamethasone in relapsed/refractory multiple myeloma refractory to pomalidomide and/or anti-CD38 monoclonal antibody-primary and subgroup analysis. Hemasphere. 2020;4(S1):abstract EP 945.
   Google Scholar
• Larocca A, Richardson PG, Oriol A, et al. HORIZON (OP-106): melflufen plus dexamethasone in patients with relapsed/refractory multiple myeloma-age subgroup analysis of elderly patients. Blood. 2020;136(Suppl 1):abstract 2293. doi:10.1182/blood-2020-136856
   Web of Science ®Google Scholar
• Mateos M-V, Oriol A, Larocca A, et al. HORIZON (OP-106): melflufen plus dexamethasone in patients with relapsed/refractory multiple myeloma with high-risk cytogenetics-subgroup analysis. Blood. 2020;136(Suppl 1):abstract 3237. doi:10.1182/blood-2020-136002
   Web of Science ®Google Scholar
• Richardson PG, Mateos M-V, Oriol A, et al. HORIZON (OP-106): melflufen plus dexamethasone in 55 patients with relapsed/refractory multiple myeloma with extramedullary disease (EMD)-subgroup analysis. Blood. 2020;136(Suppl 1):abstract 3214. doi:10.1182/blood-2020-137118
   Web of Science ®Google Scholar
• Rodriguez-Otero P, Mateos M-V, Oriol A, et al. HORIZON (OP-106): melflufen plus dexamethasone in patients with relapsed/refractory multiple myeloma exposed to prior alkylator therapy-subgroup analysis. Blood. 2020;136(Suppl 1):abstract 2321. doi:10.1182/blood-2020-136466
   Web of Science ®Google Scholar
• Ocio EM, Efebera YA, Hajek R, et al. ANCHOR (OP-104): melflufen plus dexamethasone and daratumumab or bortezomib in relapsed/refractory multiple myeloma refractory to an IMiD and/or a proteasome inhibitor-updated efficacy and safety. Blood. 2020;136(Suppl 1):abstract 417. doi:10.1182/blood-2020-135991
   Web of Science ®Google Scholar
• Bjorklund CC, Kang J, Amatangelo M, et al. Iberdomide (CC-220) is a potent cereblon E3 ligase modulator with antitumor and immunostimulatory activities in lenalidomide- and pomalidomide-resistant multiple myeloma cells with dysregulated CRBN. Leukemia. 2020;34:1197–1201. doi:10.1038/s41375-019-0620-8
   PubMed Web of Science ®Google Scholar
• Lonial S, Van de Donk N, Popat R, et al. A phase 1b/2a study of the CELMoD Iberdomide (CC-220) in combination with dexamethasone in patients with relapsed/refractory multiple myeloma. Clin Lymphoma Myeloma Leuk. 2019;19:abstract e52–e53. doi:10.1016/j.clml.2019.09.080
   Web of Science ®Google Scholar
• Van de Donk N, Popat R, Larsen J, et al. First results of iberdomide (IBER; CC-220) in combination with dexamethasone and daratumumab or bortezomib in patients with relapsed/refractory multiple myeloma. Blood. 2020;136(Suppl 1):abstract 724. doi:10.1182/blood-2020-137743
   Web of Science ®Google Scholar
• Hansen JD, Correa M, Nagy MA, et al. Discovery of CRBN E3 ligase modulator CC-92480 for the treatment of relapsed and refractory multiple myeloma. J Med Chem. 2020;63:6648–6676. doi:10.1021/acs.jmedchem.9b01928
   PubMed Web of Science ®Google Scholar
• Richardson PG, Vangsted AJ, Ramasamy K, et al. First-in-human phase 1 study of the novel CELMoD agent CC-92480 combined with dexamethasone in patients with relapsed/refractory multiple myeloma (RRMM). J Clin Oncol. 2020;38(Suppl.):abstract 8500. doi:10.1200/JCO.2020.38.15_suppl.8500
   Google Scholar
• Imbruvica (Ibrutinib) capsules, for oral use (package insert). Sunnyvale, CA: Pharmacyclis LLC; 2019.
   Google Scholar
• Tai YT, Chang BY, Kong SY, et al. Bruton tyrosine kinase inhibition is a novel therapeutic strategy targeting tumor in the bone marrow microenvironment in multiple myeloma. Blood. 2012;120:1877–1887. doi:10.1182/blood-2011-12-396853
   PubMed Web of Science ®Google Scholar
• Richardson PG, Bensinger WI, Huff CA, et al. Ibrutinib alone or with dexamethasone for relapsed or relapsed and refractory multiple myeloma: phase 2 trial results. Br J Haematol. 2018;180:821–830. doi:10.1111/bjh.15058
   PubMed Web of Science ®Google Scholar
• Chari A, Corbnell RF, Gasparetto C, et al. Final analysis of a phase 1/2b study of ibrutinib combined with carfilzomib/dexamethasone in patients with relapsed/refractory multiple myeloma. Hematol Oncol. 2020;38:353–362. doi:10.1002/hon.2723
   Web of Science ®Google Scholar
• Mateos M-V, Orlowski RZ, Ocio EM, et al. Pembrolizumab combined with lenalidomide and low-dose dexamethasone for relapsed or refractory multiple myeloma: phase I KEYNOTE-023 study. Br J Haematol. 2019;186:e117–e121. doi:10.1111/bjh.15946
   PubMed Web of Science ®Google Scholar
• Badros A, Hyjek E, Ma N, et al. Pembrolizumab, pomalidomide and low-dose dexamethasone for relapsed/refractory multiple myeloma. Blood. 2017;130:1189–1197. doi:10.1182/blood-2017-03-775122
   PubMed Web of Science ®Google Scholar
• Usmani SZ, Schjesvold F, Oriol A, et al. Pembrolizumab plus lenalidomide and dexamethasone for patients with treatment-naïve multiple myeloma (KEYNOTE-185): a randomized, open-label, phase 3 trial. Lancet Hematol. 2019;6:e448–e458. doi:10.1016/S2352-3026(19)30109-7
   PubMed Web of Science ®Google Scholar
• Mateos M-V, Blacklock H, Schjesvold F, et al. Pembrolizumab plus pomalidomide and dexamethasone for patients with relapsed or refractory multiple myeloma (KEYNOTE-183): a randomized, open-label, phase 3 trial. Lancet Hematol. 2019;6:e459–e469.
   PubMed Web of Science ®Google Scholar
• Neuse CJ, Lomas OC, Schliemann C, et al. Genome instability in multiple myeloma. Leukemia. 2020;34:2887–2897. doi:10.1038/s41375-020-0921-y
   Web of Science ®Google Scholar
• Walker BA, Boyle EM, Wardell CP, et al. Mutational spectrum, copy number changes, and outcome; results of a sequencing study of patients with newly diagnosed myeloma. J Clin Oncol. 2015;33:3911–3920. doi:10.1200/JCO.2014.59.1503
   PubMed Web of Science ®Google Scholar
• Raje N, Chau I, Hyman DM, et al. Vemurafenib in patients with relapsed refractory multiple myeloma harboring BRAFV600 mutations: a cohort of the histology-independent VE-BASKET Study. JCO Precis Oncol. 2019;3:PO.18.00266. doi:10.1200/PO.18.00266
   Web of Science ®Google Scholar
• Heuck CJ, Jethava Y, Khan R, et al. Inhibiting MEK in MAPK pathway-activated myeloma. Leukemia. 2016;30:976–980. doi:10.1038/leu.2015.208
   PubMed Web of Science ®Google Scholar
• Schjesvold F, Ribrag V, Rodriguez-Otero P, et al. Safety and preliminary efficacy results from a phase Ib/II study of cobimetinib as a single agent and in combination with venetoclax with or without atezolizumab in patients with relapsed/refractory multiple myeloma. Blood. 2020;136(Suppl 1):abstract 295. doi:10.1182/blood-2020-135845
   Web of Science ®Google Scholar
• Flynt E, Bisht K, Sridharan V, et al. Prognosis, biology, and targeting of TP53 dysregulation in multiple myeloma. Cells. 2020;9:287. doi:10.3390/cells9020287
   PubMed Web of Science ®Google Scholar
• Touzeau C, Dousset C, Le Gouill S, et al. The bcl-2 specific BH3 mimetic ABT-199: a promising targeted therapy for t(11;14) multiple myeloma. Leukemia. 2014;28:210–212. doi:10.1038/leu.2013.216
   PubMed Web of Science ®Google Scholar
• Touzeau C, Maciag P, Amiot M, Moreau P. Targeting bcl-2 for the treatment of multiple myeloma. Leukemia. 2018;32:1899–1907. doi:10.1038/s41375-018-0223-9
   PubMed Web of Science ®Google Scholar
• Kumar S, Kaufman JL, Gasparetto C, et al. Efficacy of venetoclax as targeted therapy for relapsed/refractory t(11;14) multiple myeloma. Blood. 2017;130:2401–2409. doi:10.1182/blood-2017-06-788786
   PubMed Web of Science ®Google Scholar
• Kaufman JL, Gasparetto C, Mikhael J, et al. Phase 1 study of venetoclax in combination with dexamethasone as targeted therapy for t(11;14) relapsed/refractory multiple myeloma. Blood. 2017;130:3131.
   Google Scholar
• Moreau P, Chanan-Khan A, Roberts AW, et al. Promising efficacy and acceptable safety of venetoclax plus bortezomib and dexamethasone in relapsed/refractory MM. Blood. 2017;130:2392–2400. doi:10.1182/blood-2017-06-788323
   PubMed Web of Science ®Google Scholar
• Kumar SK, Harrison SJ, Cavo M, et al. Venetoclax or placebo in combination with bortezomib and dexamethasone in patients with relapsed or refractory multiple myeloma (BELLINI): a randomized, double-blind, multicenter, phase 3 trial. Lancet Oncol. 2020;21:1630–1642. doi:10.1016/S1470-2045(20)30525-8
   PubMed Web of Science ®Google Scholar